Inflammasomes are intracellular protein complexes that activate immune responses in response to infection or detection of endogenous “danger” signals. Formation of the NLRP3 inflammasome activates caspase-1, enabling the production of mature cytokines such as interleukin-1β (IL-1β), and is implicated in pathological inflammatory responses in the periphery and the brain. Dopamine is both a neurotransmitter and a peripheral chemical mediator, and dopamine receptors are present on most types of immune cells. Yan et al. found that dopamine or a dopamine receptor 1 (DRD1) agonist inhibited NLRP3-mediated activation of caspase1 and release of IL-1β from primed bone marrow–derived macrophages (BMDMs). Dopamine was ineffective in BMDMs from Drd1-/- mice or if DRD1 was knocked down. Dopamine or the DRD1 agonist stimulated the ubiquitylation and autophagosomal degradation of NLRP3, responses that required DRD1-mediated stimulation of adenylate cyclase and adenosine 3′,5′-monophosphate (cAMP). Unexpectedly, pharmacological analysis suggested that neither protein kinase A nor the cAMP-regulated guanine nucleotide exchange factor EPAC were involved. Immunoprecipitation analysis suggested that cAMP may bind directly to NLRP3. Mass spectrometry analysis identified 3 candidate E3 ubiquitin ligases, and knockdown experiments indicated that one of these, MARCH7, was required for the dopamine-induced ubiquitylation and degradation of NLRP3. Nlrp3-/- mice were protected from MPTP-induced loss of nigral dopaminergic neurons (a model of Parkinson’s disease), whereas Drd1-/- mice exhibited more severe loss. Caspase1 activation and IL-1β abundance in the brains of the MPTP-treated Drd1-/- mice were also increased, consistent with an anti-inflammatory effect of dopamine in the brain through the suppression of NLRP3 activation. Administration of a DRD1 agonist prior to MPTP reduced loss of dopaminergic neurons, IL-1β abundance, and caspase1 activation. Induction of inflammatory responses in the periphery were also blunted by dopamine in response to lipopolysaccharide or peritoneal injection of monosodium urate, and this anti-inflammatory effect required DRD1 and was associated with reduced IL-1β and induction of NLRP3 ubiquitylation and degradation. Thus, agonists of DRD1 may be an effective strategy for limiting pathological inflammation.